Predictors of the onset of neonatal sepsis at the Neonatal Intensive Care Unit of a tertiary hospital in Ghana: A cross‐sectional study

Abstract Background and Aim Neonatal sepsis is a systemic inflammatory response to infection during the first 4 weeks of an infant's life. It is a significant cause of neonatal morbidity and mortality in low‐ and middle‐income countries. This study aimed to determine the predictors of the onset of sepsis at the Neonatal Intensive Care Unit of the Tamale Teaching Hospital, Ghana. Methods A cross‐sectional study was conducted among 275 mothers and their singleton neonates diagnosed clinically with sepsis. A univariate and multivariate logistic regression analysis adjusted for maternal occupational status was performed to determine the maternal and neonatal predictors of early‐onset (EOS) and late‐onset sepsis (LOS), respectively. Results Single motherhood (AOR = 1.882, 95% CI = 0.926−3.822, p = .08) and home delivery (AOR = 3.667, 95% CI = 0.584−23.026, p = .17) were predictors of EOS, with single motherhood being the predictor for LOS (AOR = 2.906, 95% CI = 0.715−11.805, p = .14) in a univariate analysis. When maternal occupation was adjusted for in a multivariate analysis, single mother (AOR = 2.167, 95% CI = 1.010−4.648, p = .04) was the main predictor of EOS, with low neonatal birth weight being the main predictor of LOS (AOR = 0.193, 95% CI = 0.038−0.971, p = .04). Conclusion Maternal marital status is a significant predictor of both EOS and LOS, with predictors of EOS being lower gestational age and low birth weight, while for LOS, low birth weight is the main predictor. Findings from this study can serve as a commencement point for developing predictive models for the onset of sepsis in neonates in the study facility.

Neonatal sepsis is the systemic inflammatory response to bacterial infection during the first 28 days of an infant's life.
[4] Reports from many Sub-Saharan African countries indicate varying prevalence and factors regarding neonatal sepsis. 2 However, notable factors associated with neonatal sepsis-related morbidity and mortality may include unhygienic delivery places, unsafe delivery, inappropriate cord care practices, and inadequate or lack of antenatal. 2,5,6ditionally, inadequate or lack of antenatal care may lead to failure or delay in identifying newborns at risk of neonatal sepsis for immediate clinical attention. 4Similarly, home deliveries that are poorly supervised or unsupervised, prematurity with its associated low birth weight, and failure to practise exclusive breastfeeding have been identified as risk factors associated with neonatal sepsis. 7Institutionally, poor infrastructure, health systems failure, inadequate logistics, poor maternal and child welfare intervention coverage among lowincome earners, and weak economies underpin the increase in infection rates and sepsis-related deaths. 8onatal sepsis is broadly classified into two categories based on onset time.Early-onset sepsis (EOS) when the sepsis occurs within the first 7 days of life, and late-onset sepsis (LOS) if it occurs after 7 days postnatally. 9The case severity of sepsis tends to vary between developing and developed countries.In developed countries, EOS is more severe, with a higher case mortality rate, while LOS is mostly associated with lower morbidity and mortality in the same settings. 10However, in developing countries, case fatality for LOS has been reported to be higher than EOS. 11 terms of causes associated with the onset of sepsis, conditions such as premature membrane rupture, maternal urinary tract infection, and meconium-stained amniotic fluid have been associated with EOS's aetiology. 12While, the failure of early breastfeeding initiation, prolonged parenteral nutrition, hospitalization, surgery, long-term use of invasive procedures such as intravascular catheterization and mechanical ventilation, and underlying cardiovascular and respiratory diseases had been reported as possible risk factors in the etiology of LOS. 13 Neonatal sepsis presents with nonspecific clinical signs and symptoms, and it is regarded as a medical emergency necessitating empirical treatment with or without laboratory confirmation in resource-limited settings. 14Such empirical treatment inadvertently exposes these neonates to antibiotics that otherwise may not be needed in some circumstances, contributing to antimicrobial resistance. 15Identifying neonates at a higher risk of sepsis and providing early intervention is one of the primary keys to reducing child morbidity and mortality to achieve Goal 3 of the Sustainable Development Goals. 16This study, therefore, determined the maternal and neonatal predictors of the onset of sepsis among neonates admitted to the Neonatal Intensive Care Unit (NICU) of the Tamale Teaching Hospital (TTH), Ghana.

| Study area
The study was conducted at the NICU of the TTH, Ghana.Tamale is the largest city and the only metropolitan area in northern Ghana.The TTH is the only tertiary referral hospital in northern Ghana and serves as a training center for health care institutions in its catchment area.The TTH has eight clinical Departments, including the Pediatrics and Child Health Department, of which the NICU is a subunit.The NICU is a 50-crib/incubator capacity and a seven-bed Kangaroo Mother unit with one consultant pediatrician, two medical officers, three pediatric nurses and 37 general nurses, and it provides advanced and specialized health care to neonates. 17

| Study population and design
This cross-sectional study was conducted from January 2020 to June 2021 among mothers and their neonates (≤28 days) admitted to the NICU.All neonates who were clinically diagnosed as having sepsis by the attending clinician using the WHO guidelines for sepsis screening and in collaboration with the definition of septicaemia by the International Pediatric Sepsis Conference 18,19 as part of the established protocol at the facility were recruited into the study.
Mothers/neonates without complete information in their medical records books were excluded from the study.

Key points
What is known: Neonatal sepsis is a medical emergency.
What is new: Predictors for the identification of early and late-onset sepsis in a resource-poor setting have been identified in this study.
The clinical implications of this study: Findings from this provide a valuable reference for the early identification of neonatal sepsis to improve clinical outcomes.Also, the findings in this study will serve as a commencement point for developing predictive models for identifying the onset of sepsis in neonates in resource-poor settings in Sub-Saharan Africa.

| Sampling technique and sample size determination
A purposive sampling technique was employed to select mothers and their neonates for the study. 18,19Cochran's formula 20 and an estimated septicaemia prevalence of 21.9%, as Labi, Obeng-Nkrumah 21 reported among neonates in a tertiary health facility in Ghana, were used to estimate the minimum sample size of 262, of which 10% was added for attrition.

| Data collection tool
A self-designed data collection tool was used to collect maternal sociodemographic data such as age, marital status, educational status, and occupation.Neonatal clinical records such as the onset of sepsis, age on admission, birth weight, gestational age, duration of hospitalization, the axillary temperature on admission and place of delivery were extracted as recorded in the medical records books of mothers/neonates.Neonatal birth weight was classified as low birth weight (<2.5 kg), normal birth weight (2.5−4.0 kg), and high birth weight (>4.0 kg). 22The gestational age of the neonates was categorized as preterm (delivered < 37 completed weeks of gestation) and term (delivered ≥ 37 completed weeks of gestation). 22The axillary temperature of neonates on admission was defined as hypothermia (<36.5°C),normothermia (36.5°C−37.5°C),and hyperthermia (>37.5°C). 23The place of delivery was categorized as home if delivery occurred in the house, primary if delivery happened in a primary health center, secondary if delivered at a secondary health facility and tertiary if the birth occurred in a tertiary health facility.Neonatal sepsis was defined as EOS if it occurred within the first 7 days of life and LOS if it occurred 7 days after birth. 24elf-employed (Table 1).
Statistically, there was a significant association between the duration of stay at the unit and the type of sepsis, with neonates admitted with LOS (5.9 ± 9.0 days) spending more days than those admitted with EOS (2.9 ± 2.3 days).Neonates admitted with LOS had a higher mean axillary temperature (37.0 ± 1.6°C) than those admitted with EOS (36.1 ± 3.9°C).A significant proportion of neonates with EOS (χ 2   characteristics and neonatal clinical variables as predictors of EOS. Neonates delivered by single mothers were approximately two times more likely to present with EOS (AOR = 1.882, 95% CI = 0.926−3.822,p = .08),with neonates delivered at home being approximately four times more likely (AOR = 3.667, 95% CI = 0.584−23.026,p = .17)to be admitted with EOS though this was not stat significant.When maternal occupation was adjusted for in a multivariate analysis, neonates delivered by single mothers were twice as likelier to be admitted with EOS, although marginally significant (AOR = 2.167, 95% CI = 1.010−4.648,p = .04).and Adatara et al. 29 It must be noted that the mean maternal age reported in this study was within the range (28.0 ± 6.0 years) as earlier reported among a similar cohort of Ghanaian women by Aku et al. 28 Also, findings from this study, in which the majority of the mothers

Presented in
All complete data were entered into Statistical Package for the Social Science (SPSS) v23 (IBM Corp, USA) and Microsoft Office Excel, 2019 (Microsoft, USA) for data analysis.Continuous variables were presented as means ± standard deviation and categorical variables were presented as frequencies and percentages.Student t-test and χ 2 were used to test for association between study variables where appropriate.A univariate and multivariate logistic regression analysis adjusted for maternal occupational status was performed to determine the maternal and neonatal predictors of early and LOS among neonates.A p-value of <.05 was set as the significance level for all statistical tests.3| RESULTS3.1 | Maternal sociodemographic characteristicsIn all, 275 mothers with a mean age of 26.5 ± 4.3 years and their singleton neonates participated in the study.Sixty-eight percent (187/275) of the mothers were within the age group of 20−29 years, 26.2% (72/275) were aged > 29 years and 5.8% (16/275) were aged < 20 years.Most (82.5% [227]) of these mothers were married, with 45.8% (126) having no formal education and 57.8% (159) being [3, N = 218] = 0.46, p < .001)and LOS (χ 2 [3, N = 57] = 2.82, p < .000)were born at the TTH.The mean T A B L E 1 Maternal sociodemographic characteristics.
Clinical variables of neonates stratified by the onset of sepsis.
number of conditions clinically diagnosed for all the neonates was 1.5 ± 0.8.Neonates who were admitted with EOS had a statistically significantly lower number of clinical diagnoses conditions (χ 2 [3, N = 218] = 1.27, p < .000)comparedwithneonateswithLOS (Table2).3.3 | Predictors of the onset of sepsis among neonates admitted to the NICU, TTHPresented in Table 3 is a univariate and multivariate logistic regression analysis to determine maternal sociodemographic T A B L E 2

Table 4
Univariate and multivariate logistic regression analysis of maternal and neonatal predictors of early-onset of sepsis among neonates admitted to the NICU, TTH.
In this study, the marital status of mothers, lower gestational age and low birth weight were the main predictors of the onset of neonatal sepsis.These will provide a valuable local reference for the influence of maternal age on neonatal admissions into NICUs in Ghana, which is consistent with earlier reports byAku et al.
T A B L E 4 Univariate and multivariate logistic regression analysis of maternal and neonatal predictors of late-onset sepsis among neonates admitted to the NICU, TTH.